C49-25 Oh No, My Hand, Foot, and Lenvatinib Use

Introduction Lenvatinib is an oral multi-kinase inhibitor that targets vascular endothelial growth factor receptors (VEGFR1-3), fibroblast growth factor receptors (FGFR1-4), platelet-derived growth factor receptor alpha (PDGFRα), RET, and KIT. By disrupting angiogenesis and tumor proliferation, it is used in hepatocellular carcinoma, renal cell carcinoma, and differentiated thyroid carcinoma. Despite its efficacy, lenvatinib is associated with significant adverse effects. In recurrent thyroid cancer, palmar-plantar erythrodysesthesia (PPE) or hand-foot syndrome occurs in over 30% of patients¹, while arterial thromboembolic events such as myocardial infarction and stroke occur in approximately 2-3%, typically in those with preexisting vascular risk factors². Case Presentation A 69-year-old woman with a history of hypertension, hyperlipidemia, and metastatic recurrent thyroid cancer status post-thyroidectomy (2015) presented with new neurological symptoms 24 hours after discharge for a recent cerebrovascular accident involving bilateral cerebral lobes, right greater than left. Lenvatinib had been discontinued two weeks prior to this admission. Laboratory findings showed mild anemia (hemoglobin 10.1 g/dL) and mild hyponatremia (Na 133 mmol/L) with otherwise normal metabolic and coagulation profiles. Imaging demonstrated new acute ischemia in the right thalamus and evolving multifocal bilateral infarcts. Chest X-ray and vascular duplex ultrasound were unremarkable. Examination revealed erythematous, tender plaques on the finger tips, palms and soles consistent with hand-foot syndrome³. Discussion The concurrent development of palmar-plantar erythrodysesthesia and multifocal ischemic stroke highlights lenvatinib’s systemic vascular toxicity. Inhibition of VEGFR, FGFR, and PDGFR pathways disrupts endothelial integrity, induces inflammation, and promotes a prothrombotic state2,4. While either complication alone is recognized, their co-occurrence is rare and may represent different manifestations of the same endothelial injury cascade. This case provides clinical evidence that visible cutaneous toxicity could serve as an early external marker of systemic vascular dysfunction that, if unrecognized, may culminate in serious cerebrovascular events3,5. This case underscores the potential for severe vascular complications during lenvatinib therapy and suggests that dermatologic toxicity may signal underlying endothelial injury. Vigilant monitoring for neurologic symptoms in patients who develop hand-foot syndrome, along with aggressive management of hypertension and vascular risk factors, may help prevent life-threatening ischemic events. Early recognition and reporting of such cases are crucial to improve patient safety and refine monitoring guidelines for anti-angiogenic tyrosine kinase inhibitors3,6.